|Chromosome disorders and gene abnormalities|
|Single Gene AD||Adult PKCD
|Single Gene Disorders AR||Cystic Fibrosis
|Single gene X-linked||Duchenne Muscular Dystrophy
|X linked recessive|
|X linked dominant|
|XXX||Triple X syndrome|
|abnormal chromosome numbers|
|abnormal chromosome structures|
Bernard J.A. Marfan in 1896.
Connective tissue disease affecting skeleton, eyes, heart, lungs and blood vessels.
Caused by a mutation in the gene for fibrillin 1 on chromosome 15.
75% of cases are inherited, 25% spontaneous mutation.
Each child of an affected parent has a 50% chance of inheriting MFS.
Affects both men and women of any ethnic group.
10,000 patients in UK (incidence approx. 1 in 5,000)
|Skeletal||Tall thin physique, disproportionately long limbs, fingers and toes, lax
ankles, flat feet, spinal curvature, abnormally shaped narrow chest (with pigeon or funnel deformity), armspan usually greater than height, joint hypermobility or contractures and dislocations, striae. Dilatation of the lumbar dural sac (75% of patients). Hernias are common.
|Cardiovascular||Dilatation of ascending and sometimes descending aorta, incompetence of aortic and mitral valves, aneurysm and dissection of aorta.|
emphysema and asthma
|Ocular||Lens subluxation /dislocation, myopia and unstable refraction, detachment of retinal detatchment, squint, glaucoma|
|Dental||High-arched palate, crowding of teeth.|
Small stature with shortened limbs with normal trunk length.
Apparent prominence of skull with prominent forehead and saddle nose.
Kyphosis. Small hands with fingers of equal length.
1 gene affected 2 genes affected alpha thalassaemia traitmay be symptoms of mild anaemia.
If two people with the alpha thalassaemia trait have a child, there is a one-in-four chance that their child will inherit the most severe form of alpha thalassaemia3 genes affected Haemoglobin H disease.H disease will have lifelong (chronic) anaemia, and may require regular blood transfusionsAll four genes affectedalpha thalassaemia major. Infants with this condition are unable to produce normal haemoglobin and are unlikely to survive pregnancy. There have been some cases of unborn babies being treated with blood transfusions while still in the womb, but this type of treatment has a low success rate.
|1 gene affected|
|2 genes affected||alpha thalassaemia trait||may be symptoms of mild anaemia.
If two people with the alpha thalassaemia trait have a child, there is a one-in-four chance that their child will inherit the most severe form of alpha thalassaemia
|3 genes affected||Haemoglobin H disease.||H disease will have lifelong (chronic) anaemia, and may require regular blood transfusions|
|All four genes affected||alpha thalassaemia major||Infants with this condition are unable to produce normal haemoglobin and are unlikely to survive pregnancy. There have been some cases of unborn babies being treated with blood transfusions while still in the womb, but this type of treatment has a low success rate.|
Laurence Moon Biedl Syndrome
AD. dwarfism obesity polydactyly or syndactyly genital hypoplasia and poorly developed secondary sexual characteristics. Mental defeciency, retinitis pigmentosa and optic atrophy.
|X linked Single Gene Disorders|
|Duchenne Muscular Dystrophy|
Small stature. Brachycephalic flat expressionless face. slanted eyes with epicanthic folds. +/- convergent squint. Saffle nose prominent tongue. Small broad hands with single palmar crease, small fingers , curved short little finger. CHD eg ASD.
Three types of Down’s syndrome
Regular trisomy 21 (94%) all the cells have an extra chromosome 21.
Translocation (4%) the extra chromosome 21 material is attached to another chromosome and one of the parents may carry the translocated chromosome without any signs of the condition themselves.
Mosaic (2%) only some of the cells have an extra chromosome 21 tends to result in milder features.
X linked chromosomal abnormality causing varying degress of learning disabilities
More common and more severe in males
Turner Syndrome Support Society UK
Chromosome abnormality affecting only females, caused by the complete or partial deletion of the X chromosome. Commonest cause of primary ovarian failure. May also be mosaics 46 XX 47XXX.
Incidence approximately 1:2000 live female births.
Confirmation of a diagnosis of TS is by karyotype but a suspected diagnosis can be made by a series of characteristic physical features
broad chest and widely spaced nipples (shield chest)
increased carrying angle of the elbows
short 4th metacarpal
Coarctation of aorta
Two main clinical features of TS are short stature and non-functioning ovaries.
Diagnosis can be made at birth
eg newborn needs heart surgery because of coarctation of the aorta
or because of oedema of the hands and feet.
Pre-natal diagnosis is sometimes made by chorionic villous sampling, amniocentesis or ultra sound.
However, most girls are diagnosed in early childhood when growth fails or later when the absence of a pubertal growth spurt and development of secondary sexual characteristics become apparent.
Tall stature with long legs.
Small firm testes
Mitochondria contain their own set of genes (in addition to the genes in the cell’s nucleus).
Mitochondrial DNA mutations cause several well recognised disorders, often associated with neuromuscular features.
A person inherits his or her mitochondria from the egg and not the sperm.
Therefore, mitochondrial inheritance gives a pattern of the condition affecting males and females, but always inherited from a mother.
An affected male does not pass on his mitochondria to his children, so all his children will be unaffected.